Inter- and intramolecular hydroamination of unactivated alkenes catalysed by a combination of copper and silver salts: The unveiling of a Bronstedt acid catalysis

Article abstract of DOI:10.1002/adsc.201000536

The combined use of a copper halide, a silver salt and a phosphane ligand was applied for the catalysis of inter- and intramolecular hydroamination of alkenes. The reactions of unactivated olefins with nitrogen substrates were investigated. Mechanistic investigations demonstrated that the catalytic system generated a Bronsted acid which appeared to be the prominent catalytic species. Copyright

Full text of DOI:10.1002/adsc.201000536

FULL PAPERS
DOI: 10.1002/adsc.201000536
Inter- and Intramolecular Hydroamination of Unactivated
Alkenes Catalysed by a Combination of Copper and Silver Salts:
The Unveiling of a Brønstedt Acid Catalysis
Christophe Michon,a,b,c,* Florian Medina,a,b,c Frꢀdꢀric Capet,a,b,d Pascal Roussel,a,b,d
and Francine Agbossou-Niedercorna,b,c,
*
a
Universitꢀ Lille Nord de France, 59000 Lille, France
CNRS, UCCS UMR 8181, 59655 Villeneuve d’Ascq, France
ENSCL, CCCF, (Chimie-C7) BP 90108, 59652 Villeneuve d’Ascq Cedex, France
Fax : (+33)-3-2043-6585; e-mail: christophe.michon@ensc-lille.fr or , francine.agbossou@ensc-lille.fr
ENSCL, CS, (Chimie-C7) BP 90108, 59652 Villeneuve d’Ascq Cedex, France
Fax : (+33)-3-2043-6814 (for X-ray diffraction information); e-mail: pascal.roussel@ensc-lille.fr
b
c
d
Received: July 8, 2010; Revised: September 19, 2010; Published online: December 7, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000536.
Abstract: The combined use of a copper halide, a alytic system generated a Brønsted acid which ap-
silver salt and a phosphane ligand was applied for peared to be the prominent catalytic species.
the catalysis of inter- and intramolecular hydroami-
nation of alkenes. The reactions of unactivated ole-
fins with nitrogen substrates were investigated. Keywords: alkenes; Brønsted acid; copper; hydroa-
Mechanistic investigations demonstrated that the cat- mination; silver salts
Introduction
Recently, group 11 metals have been highlighted by
various contributions. The usefulness of gold was
Amines are ubiquitous in natural products, building pointed out on alkene[7] and allene[8] substrates for
blocks or targets for fine chemicals, farming-related both intra- and intermolecular hydroamination reac-
chemicals and biologically active compounds.[1] The tions as well as for diaminations. Silver was recently
hydroamination of unactivated alkenes is the shortest shown to be active for the hydroamination of al-
synthetic route to secondary and tertiary amines. This kenes.[9] Copper was successfully used for diamina-
atom-economic reaction can be performed on unacti- tion[10] and carboamination[11] reactions, but it was less
vated alkenes according to three methods: radical applied for hydroamination. Hii et al. reported on the
transfer,[2], metal catalysis[1,3,4] and acid catalysis.[4,5,6] use of copper triflates in intermolecular reactions be-
The last-mentioned method can imply a pure Brøn- tween vinylarenes and amines.[12] Gunnoe et al. ap-
stedt acid[5,6] or the combination of a metal and an plied NHC-Cu-amido complexes to the intermolecu-
acid.[3] For the enantioselective synthesis of optically lar addition of amines to activated olefins.[13] Recently,
pure amines, the most studied and privileged hydroa- Sawamura et al. reported the efficiency of a copper
mination method is metal catalysis. Lanthanides and alkoxide catalyst in various intramolecular hydroami-
actinides (f block) were widely screened and signifi- nation reactions.[14]
cant achievements were reported for intramolecular
Following the past interest of some of us on amina-
reactions. By comparison, applications in asymmetric tion reactions,[15] we started studying the use of
catalysis of transition metals from groups 3–11 (d copper catalysts in hydroamination. Initially, alkene
block) remain scarce and that is where the hydroami- coordination to copper complexes was extensively
nation challenge seems to be. Moreover, the develop- studied[16] for various applications like biomimetic
ment of recoverable catalysts may favour group 3–11 models for the ethylene receptor site of plants.[17] In-
metals which may form stable and easy to handle or- terestingly, Okamoto et al.[18] used copper halide com-
ganometallic catalysts.
plexes for the catalysed intramolecular hydroamina-
tion of allenylamines.
Adv. Synth. Catal. 2010, 352, 3293 – 3305
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3293

Christophe Michon et al.
FULL PAPERS
Relying on the Dewar–Chatt–Duncanson model of versions (Table 2). Activity decreased accordingÀto
À
olefin bonding,[19] the activation of alkenes by metals the order: SbF6À >TfOÀ @PF6
> >
NTf2À @ClO4
can be rationalised. We assumed that copper cationic BF4À @BARFÀ. Surprisingly, BARFÀ salts led to poor
or dicationic species coordinated to p-acceptor li- conversions (entries 9 and 10). The silver cation con-
gands would exhibit reduced p-back-donation on the firmed to be the most appropriate as compared to al-
coordinated olefins which would consequently be kaline-earth salts (entries 2 and 9). As expected, no
more reactive. Hence, such cationic copper catalysts conversion was observed using silver benzoate
would be of interest for hydroamination reactions.
(entry 7), the benzoate anion coordinating most prob-
Herein, we would like to report on our investiga- ably to copper.[21]
tions of the combined use of phosphanes, copper hal-
Among the various solvents screened (Table 3),
ides and silver salts applied to the catalysis of inter- 1,1’,2,2’-tetrachloroethane (entries 5 and 6) showed to
and intramolecular hydroamination reactions.
Table 2. Silver and related salts screening.
Results and Discussion
Reactivity Studies
The reaction of norbornene with tosylamine was used
as a model to optimise the experimental conditions,
the exo-addition product[20] 3a (Table 1) being formed
selectively. Regarding the metal source, copper(II)
bromide led to higher conversion than copper(II)
chloride when AgBF4 was used. The use of a glove-
box for transfers improved drastically the yields, dem-
onstrating the negative impact of water. Then, various
phosphane ligands were screened (Table 1). 1,2-Bis-
Entry
AgX
Conversion[a] [%]
1
2
3
4
5
6
7
8
9
10
AgBF4
NaBF4
AgPF6
AgSbF6
AgOTf
AgClO4
AgPhCO2
AgN(Tf)2
KBARF
AgBARF
47
0
75
>95
95
45
0
68
9
5
ACHTUNGTRENNUNG(diphenylphosphino)ethane, e.g., dppe (entry 4),
showed to be the most efficient, even if conversion
was higher without the use of any phosphane ligand
(entry 7).
Screening of silver(I) salts confirmed that the less
coordinating the anion was, the higher were the con-
[a]
Conversion determined by GC. Average of 2 runs.
Table 3. Solvent screening.
Table 1. Phosphane ligand screening.
Entry Solvent
T [8C] Conversion[a] [%]
1
2
3
4
5
6
7
8
toluene
toluene
60
25
60
25
90
70
95
85
>95
>95
>95
25
–
5
Entry
Ligand
(OPh)3
P(Ph)3
PCy3
dppe
dppeO
dppb
–
Loading [mol%]
Conversion [%][a]
1
2
3
4
5
6
7
8
PG
10
10
10
5
5
5
5
30
–
1,2-dichloroethane
1,2-dichloroethane
1,1’,2,2’-tetrachloroethane 25
1,1’,2,2’-tetrachloroethane 60
dichloromethane
chloroform
diethyl ether
THF
80
20
5
>95
18
16
34
0
25
25
25
60
60
60
60
–
9
P
E
10
10
5
10
11
12
13
9
10
11
P
T
DME
CH3CN
1,4-dioxane
30
70
80
Xantphos
Davephos
5
[a]
[a]
Conversion determined by GC.
Conversion determined by GC.
3294
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 3293 – 3305

Inter- and Intramolecular Hydroamination of Unactivated Alkenes
Table 4. Olefin reactivities with tosylamine.
Entry Alkene (1a–j) Copper salt (mol%) Silver salt (mol%) Time [h] Temperature [8C] Isolated yield[a] [%] of 3a–j
1
CuBr2 (5)
CuBr (5)
AgSbF6 (10)
AgSbF6 (5)
3
20
25
100
95 (exo)[b]
95 (exo)[b]
CuBr2 (5)
CuBr (5)
AgSbF6 (10)
AgSbF6 (5)
20
20
100
100
150
90 (4/6)[c]
2
<5
2
3
CuBr2 (5)
CuBr (5)
AgSbF6 (10)
AgSbF6 (5)
100
100
150
96
57
82
4
5
6
7
8
CuBr2 (5)
CuBr (5)
AgSbF6 (10)
AgSbF6 (5)
30
20
100
100
150
50 (branched)[d]
14 (branched)[d]
20 (branched)[d]
CuBr2 (5)
CuBr (5)
AgSbF6 (10)
AgSbF6 (5)
48
20
100
100
150
88 (branched)[d]
21 (branched)[d]
25 (branched)[d]
CuBr2 (5)
CuBr (5)
AgSbF6 (10)
AgSbF6 (5)
20
24
100
100
150
16 (linear)[e]
10 (linear)[e]
0
CuBr2 (5)
CuBr (5)
AgSbF6 (10)
AgSbF6 (5)
100
100
150
0
0
0
CuBr2 (5)
CuBr (5)
AgSbF6 (10)
AgSbF6 (5)
30
20
100
150
0
0
9
CuBr2 (5)
AgSbF6 (10)
20
100
0
10
CuBr2 (5)
CuBr (5)
AgSbF6 (10)
AgSbF6 (5)
20
20
100
150
0
0
[a]
[b]
[c]
[d]
[e]
Average of 2 runs.
exo-Product as shown by NMR.
Branched/isomerised ratio of 4/6 shown by NMR (isomerization by TosNH2 addition on position 3 of n-hexene).
Branched product from Markovnikov addition.
Linear product from anti-Markovnikov addition.
be the most interesting considering its polarity and
high boiling point. Other chlorinated solvents were tosACHTUNGTRENNUNG
Next, various olefins were allowed to react with
ylamine in the presence of either copper(I) or cop-
also suitable (entries 3, 4, 7, 8) with the exception of per(II) bromide in combination with AgSbF6 and
chloroform. Toluene (entries 1 and 2) and 1,4-dioxane dppe (Table 4). As a general trend, copper(II) bro-
(entry 13) led to good conversions as well.
mide proved to be more reactive than copper(I) bro-
Adv. Synth. Catal. 2010, 352, 3293 – 3305
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3295

Christophe Michon et al.
FULL PAPERS
Table 5. Amine substrate reactivities with norbornene.
mide as reactions were requiring less time and lower
temperatures. This was observed in the case of cyclo-
hexene (entry 3) and norbornene which lead to the
exclusive formation of an exo-product (entry 1). Oth-
erwise, dihydrofuran showed no reactivity (entry 7).
Branched “Markovnikov” products were obtained for
vinylcyclohexane
(entry 4),
and
allylbenzene
(entry 5). Reaction of n-hexene (entry 2) proceeded
well with some isomerised product resulting from the
addition on position 3.[3h] With the exception of 2-vi-
nylpyridine leading to the linear “anti-Markovnikov”
product (entry 6), conjugated olefins (e.g., styrene,
1,3-cyclohexadiene, 4-vinylpyridine) did not react (en-
tries 8–10).
Entry Reagent
Time Silver
Product 5a–m
4a–m
[h]
salt
yield[a] [%]
1
2
70
AgSbF6
0
48
30
AgSbF6 72
AgBF4 80
To check the range of applicable nucleophiles, vari-
ous amine derivatives were allowed to react with nor-
bornene (Table 5). exo-Addition products were exclu-
sively formed as confirmed by NMR[20]. Benzyl and
methyl carbamates (entries 3 and 4), para-nitroaniline
(entry 5) and oxazolidone (entry 7) provided the re-
lated hydroamination products in good yields. For
amides, whereas no reactivity was noticed for acet-
amide (entry 1) and trifluoroacetamide (entry 8), ben-
zamide (entry 9) gave the hydroamination product in
modest yield and an improved conversion was found
for chloroacetamide (entry 2). Benzylamine, N,N-di-
methylurea and succinimide (entries 11, 12 and 13)
did not react, nor did phthalimide and hydrazones.
Moreover, stronger nucleophiles like morpholine, di-
n-propylamine or butylamine did not react with any
screened olefins. Finally, weak basic amines did not
react with cyclohexene (see the Supporting Informa-
tion). Hence, the range of reacting nucleophiles and
olefins proved to be quite narrow using such catalysts.
3
4
5
30
20
AgBF4 86
AgBF4 95
6
48
AgSbF6 21[b]:14[c]
AgSbF6 95
7
8
20
20
AgBF4
0
9
20; 48 AgSbF6 27;[d] 35
10
11
65
20
AgSbF6 14[e]:11[f]
Mechanistic Investigations
AgBF4
0
0
We were particularly interested by two other results.
First, benzotriazole reacted with norbornene to
afford, in moderate yields, two hydroamination prod-
ucts 5f1 and 5f2 (Table 5-entry 6 and Scheme 1). Such
a reaction implying triazole derivatives is usually per-
formed by an acid catalysis.[22]
12
20
20
AgSbF6
13
AgSbF6 0[d]
Second, the reaction between aniline and norbor-
nene led to a mixture of hydroamination and Friedel–
Crafts alkylation products, 5j1 and 5j2 (Table 5-
entry 10 and Scheme 2) without any product resulting
from a Hofmann–Martius rearrangement.[6k] Hydro-
[a]
Isolated yield, average of 2 runs.
Hydroamination product 5f1.
Rearranged product 5f2.
At 1508C.
Hydroamination product 5j1.
Arylation product 5j2.
[b]
[c]
[d]
[e]
[f]
ACHTUNGTRENNUNGarylation products like 5j2 are typical for hydro-
ACHTUNGTRENNUNG
amination reactions using an acid[5,6,23e–g] or metal-
acid[3,23a–d,f–g] catalyst. At that point, we started sus-
pecting the generation of an acid along our hydroami-
nation reactions and performed control experiments.
and AgBF4. The reaction could be stopped by the ad-
Table 6 shows the effects of additives on the hydro- dition of an inorganic base like Cs2CO3 (entry 3), an
amination reaction of norbornene with tosylamine organic base like triethylamine (entry 4) or the non-
catalysed by a combination of copper(II) bromide coordinative base 2,6-bis(tert-butyl)pyridine (entry 2).
3296
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 3293 – 3305

Inter- and Intramolecular Hydroamination of Unactivated Alkenes
calcium hydride decreased the yield to 10% (entry 6).
We should also recall that reaction did not proceed
well in THF (5% conversion, Table 3-, entry 10)
which can be considered as a Lewis basic and coordi-
nating solvent.
These results supported that some acid (HBF4) was
formed during the hydroamination reaction. The use
of a proton source like hydroquinone (entry 7) which
can reduce Cu(II) inhibited the reaction. This suggests
that the dicationic copper complex may be involved
in the reaction process. Unlike benzoquinone
(entry 8), triethylamine (entry 4) can be considered as
a reducing agent;[24b] none of these reagents allowed
the reaction to occur. Otherwise, a radical scavenger
like TEMPO (entry 9) inhibited the reaction. But
TEMPO is also known to react irreversibly with acids
by disproportionation.[24c] The addition of a proton
trap like PhSi(Me)3 (entry 10) stopped the reaction
and confirmed the presence of free protons in the re-
action medium. It is worthy of note that the reaction
proceeded well in the presence of 5 mol%
HBF4·O(Me)2 with (92% yield, entry 11) or without
(75% yield, entry 12) copper-silver salts.
Scheme 1. Reactivity of benzotriazole with norbornene.
A similar screening was carried out with cyclohex-
ene (Table 7). The hydroamination reaction of cyclo-
hexene with tosylamine catalysed by a combination of
Scheme 2. Reactivity of aniline with norbornene.
The use of a weak Lewis and Brønstedt base like phe- copper(I) bromide and AgSbF6 was also stopped by
nothiazine decreased the yield to 29% (entry 5). Phe- the addition of an inorganic or organic base (en-
nothiazine is also known as a radical polymerisation tries 2–4). Addition of calcium hydride (entry 6) scav-
inhibitor[24a] but such a property might not be applica- enged some protons and reduced the reaction yield to
ble here. Addition of another proton scavenger like 32%. The use of a proton source like hydroquinone
(entry 8) decreased the reaction yield to 23%.
Table 6. Additive effects on copper(II) and silver(I) salts-
catalysed reaction of norbornene with tosylamine.
Table 7. Additive effects on copper(I) and silver(I) salts-cat-
alysed reaction of cyclohexene with tosylamine.
Entry Additive (mol%)
Conversion[a] [%]
Entry Additive (loading mol%)
Isolated yield[a] [%]
1
no additive
47
0
0
2
3
2,6-bis(tert-butyl)pyridine (5.5)
Cs2CO3 (5)
1
none
82
0
2
Cs2CO3 (5)
4
5
6
7
8
9
10
11
12
NEt3 (5)
phenothiazine (25)
CaH2 (10)
hydroquinone (5)
benzoquinone (5)
TEMPO (5)
PhSiMe3 (1 equiv.)
HBF4·OMe2 (5)
HBF4·OMe2 (5)[b]
0
3
4
5
6
8
9
10
11
12
2,6-bis(tert-butyl)pyridine (5.5)
phenothiazine (25)
TEMPO (5)
0
0
0
32
23
0
29
10
15
2
0
0
CaH2 (10)
hydroquinone (5)
benzoquinone (5)
PhSi(Me)3 (1 equiv.)
HBF4·OMe2 (5)
HBF4·OMe2 (5)[b]
0
92
90
75[b]
50[b]
[a]
[b]
[a]
[b]
Measured by GC, average of 2 runs.
Conversion with 5 mol% HBF4 alone, without use of
Average of 2 runs.
Reaction with 5 mol% HBF4 alone, without use of
[CuBr2 +AgBF4 +dppe].
[CuBr2 +AgBF4 +dppe].
Adv. Synth. Catal. 2010, 352, 3293 – 3305
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3297

Christophe Michon et al.
FULL PAPERS
Scheme 3. Proposed reaction pathways for intermolecular hydroamination reactions.
TEMPO (entry 5), benzoquinone (entry 9) and action of norbornene with tosylamine in dichlorome-
PhSi(Me)3 (entry 10) inhibited the reaction. The reac- thane at room temperature (Scheme 4).
tion proceeded well in presence of 5 mol%
When a crude batch of 6 was used, a 40% conver-
HBF4·O(Me)2 with (90% yield, entry 11) and without sion was obtained. Repeated recrystallisations of 6
copper-silver salts (50% yield, entry 12). Hence, it led to complete deactivation of the catalyst without
was very likely some Brønstedt acid was formed any decomposition.
during the hydroamination reaction, by coordination
In a second control experiment, norbornene react-
of the nitrogen substrate to the cationic copper(II) or ed with para-nitroaniline using two types of catalysts
copper(I) complex followed by the release of a (Scheme 5). Whereas the hydroamination reaction
proton and formation of a metal-amido complex proceeded well using a one-pot combination of CuBr-
(Scheme 3). That confirmed a hypothesis which was AgSbF6-dppe, the use of isolated NHC-Cu(I) complex
previously advanced for other hydroamination reac- 7 was not successful. Hence, the involvement of such
tions performed in the presence of a Brønstedt acid an amino[13a] or amido[25] copper complex as a catalyst
source.[3c,g,6c,d,12]
was unlikely. Moreover, the reaction of norbornene
For intermolecular hydroamination reactions, two with 4-nitroaniline worked fine when catalysed by a
pathways can thus be reasonably considered after the combination of CuBr2-AgBF4-dppe or simply by
olefin protonation (Scheme 3). Pathway 1 would HBF4. For both catalysts, rates of conversion were
allow the addition of the free amine to the protonated quite similar when followed by NMR and GC (see
olefin and release of the acid catalyst, the amido- the Supporting Information). Hence, according to all
copper complex being an unactive species.
these observations, these intermolecular hydroamina-
Pathway 2 would allow the amine from copper tion reactions may proceed by following pathway 1
complex II to react with the protonated olefin releas- (Scheme 3), a Brønstedt acid catalyst being formed
ing the hydroamination product and the dicationic when the amine coordinates to the copper cationic
copper complex I.
complex.
In addition, though the screening of various enan-
To check such hypotheses, we performed control
experiments. By reacting complex I with tosylamine, tiopure phosphane ligands, no enantioselectivity was
complex 6 was isolated and used as catalyst for the re- obtained for the addition of tosylamine to norbornene
Scheme 4. Influence of amount of acid on the reaction of
norbornene with tosylamine.
Scheme 5. Comparison of catalytic activities of in-situ gener-
ated and isolated Cu(I) catalysts.
3298
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 3293 – 3305

Inter- and Intramolecular Hydroamination of Unactivated Alkenes
(see the Supporting Information). Obviously, these for amides, for example, electron-poor substrates like
catalyses were not likely to allow any asymmetric in- tosyl (entries 17 and 18), acetyl (entries 19 and 20),
duction as far as they involve the protonation of the benzoyl (entries 21 and 22) and benzyl carbamate de-
olefin before the nucleophile addition of the nitrogen rivatives (entries 23 and 24). Acid catalysis using
substrate.
HBF4·O(Me)2 improved conversions with benzyl (8b,
For intramolecular hydroamination reactions entry 5) and isobutyl derivatives (8d, entry 13). Previ-
(Table 8), the catalysis proceeded only for electron- ously, intramolecular hydroamination reactions were
rich amine substrates substituted by a benzyl (8b, en- reported to proceed efficiently with Brønstedt acid
tries 3–4, 6), a methyl (8c, entries 7–10), an isobutyl catalysts for amides[6g,i,l,o,p] or basic amines,[6c,d] metal
(8d, entries 11, 12 and 14) and a methylcyclohexane catalysts being also effective for various substrates[1].
moiety (8e, entries 15 and 16). These reactions re- In comparison to the work of Ackermann et al.,[6c,d]
quired long heating (20–30 h) at high temperatures our acid-catalysed reactions for compound 8b (en-
(130–1508C). No reactivity was observed for a pri- tries 3–6) gave quite similar results at a lower catalyst
mary amine derivative (8a, entries 1 and 2) as well as loading (5 against 10–20 mol%) but at higher temper-
ature (150 against 80–1308C). The reactivity of elec-
tron-rich substrates confirmed that an acid-catalysed
pathway is likely to take place during intramolecular
hydroamination reactions (Scheme 6).
Table 8. Intramolecular reaction screening.
Coordination of the nitrogen substrate to a cationic
Cu(II) complex would liberate an inorganic acid.
Amine would then be protonated; and a proton-ex-
change with the olefin would operate allowing the
cyclisation to occur and the proton to be released.
Attempts to isolate intermediates were difficult re-
garding the sensitivity to air and moisture of these Cu
complexes. However, diffusion of an equimolar solu-
Entry R, Reagent Conditions[a] Temp. Conversion
8a–i
[8C]
[%][b] [isolated
yield (%)] 9a–i
tion of [dppeCu]ACTHNUTRGNEUNG[SbF6]2 and norbornene in dichloro-
methane with pentane afforded highly sensitive col-
ourless single crystals. X-ray diffraction analysis
showed that the norbornene-dppeCuSbF6 complex
10[26] was formed (Figure 1). To the best of our knowl-
edge, this is the first structure determination of a
phosphane-Cu(I)-norbornene complex.
1
2
3
4
5
6
7
8
H, 8a
H, 8a
A
100
0
0
0
79
A or B or C 150
A
A
D
A
A
A
A
A
A
A
D
A
A
A
A
Bn, 8b
Bn, 8b
Bn, 8b
Bn, 8b
Me, 8c
Me, 8c
Me, 8c
Me,[c] 8c
i-Bu, 8d
i-Bu, 8d
i-Bu, 8d
i-Bu, 8d
CH2Cy, 8e
CH2Cy, 8e
Ts, 8f
100
150
150
150
100
130
150
150
100
130
130
150
130
150
100
150
100
150
100
150
100
150
91
100[c] [85]
As demonstrated previously by EPR,[24b] the pres-
ent X-ray diffraction analysis confirmed that norbor-
nene could reduce copper(II) to copper(I), the stan-
dard reduction potential of (Cu2+/Cu+) being low
(E0 =+0.159 V). The C=C double bond C3/C8 was
lengthened [1.375(5) ꢂ] as compared to the free nor-
0
40
9
80
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
100[c] [89]
10
62
82
100 [93]
41
100 [94]
0
0
0
0
0
0
0
0
Ts, 8f
A
A
B or C
A
B
Ac, 8g
Ac, 8g
Bz, 8h
Bz, 8h
CBz, 8i
CBz, 8i
A
B
[a]
Conditions A: 5 mol% CuBr2, 5 mol% dppe, 10 mol%
AgBF4. Conditions B: 15 mol% CuBr2, 15 mol% dppe,
30 mol% AgBF4. Conditions C: 5 mol% CuBr2, 5 mol%
dppe, 10 mol% AgSbF6. Conditions D: 5 mol%
HBF4·O(Me)2
[b]
[c]
Average of 2 runs. Measured by 1H NMR with 1,3,5-
(MeO)3C6H3 as internal standard.
Scheme 6. Proposed mechanism for intramolecular hydroa-
mination reactions.
30 h reaction time.
Adv. Synth. Catal. 2010, 352, 3293 – 3305
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3299

Christophe Michon et al.
FULL PAPERS
bornene[27a] [1.334(1) ꢂ] suggesting p-back-donation
from the metal to the olefin. Compound 10 showed a
weak Cu-olefin interaction as confirmed by the large
À
À
bond distances Cu P1 and Cu P2 [2.2876(8) and
À
À
2.2834(8)], as well as by the large bite angle P1 Cu
P2 [90.71(3)8], values of ca. 788 usually being found
for stable copper-olefin complexes with nitrogen li-
gands.[27b–f] This may explain the high instability of
compound 10 which decomposed readily during all
other isolation and characterisation attempts.
Otherwise, the diffusion of an equimolar solution
of [dppeCu]ACTHUNTRGNE[UNG SbF6]2 and tosylamine in dichlorome-
thane with pentane afforded colourless single crystals.
X-ray diffraction analysis showed no amido-copper
species but rather a CuACTHNUTRGNEUNG
(dppe)2SbF6 complex 11[26]
(Figure 2). Similar complexes with different anions[28]
were already characterised by X-ray determination
and compound 11 exhibited the same structural prop-
erties. First, this result confirmed the propensity of
copper(II) to be reduced to copper(I) by diphenyl-
phosphinoethane or tosylamine. Second, as previously
shown with such phosphane ligands, copper behaves
often as a hemilabile metal changing easily its coordi-
nation[29] unless bonded to strong s-donor ligands.[25]
Hence, several copper organometallics may be
formed and stay in equilibrium leading to potent cata-
lytic species.
Figure 1. Compound
10
[(dppe)Cu(norbornene)]SbF6
CH2Cl2. Thermal ellipsoids are shown at 50% level and hy-
drogen atoms are omitted for clarity.[26] Selected bond
À
À
lengths (ꢂ) and angles (8): Cu C3 2.097(3), Cu C8
À
À
À
2.108(3), Cu P1 2.2876(8), Cu P2 2.2834(8), C3 C8
À
À
À
À
À À
1.375(5), P1 Cu P2 90.71(3), C3 Cu C8 38.18(13), P1 P2
À
À
À
À
C3 C8 0.63(5), P1 C2 C1 P2 60.2(2).
Figure 2. Compound 11 [(dppe)2Cu]SbF6 CH2Cl2. Thermal ellipsoids are shown at 50% level and hydrogen atoms are omit-
ted for clarity.[26] Selected bond lengths (ꢂ) and angles (8): Cu P1 2.2906(8), Cu P2 2.2902(8), Cu P3 2.2863(8), Cu P4
À
À
À
À
À
À
À
À
À
À
À
À
À
À
À
2.2940(8), P1 Cu P2 89.22(3), P1 Cu P3 115.83(3), P2 Cu P3 120.65(3), P3 Cu P4 88.63(3), Cu P1 C1 C2 49.06(19),
À
À
À
À
À
À
À
À
À
À
À
À
À
À À
P1 C1 C2 P2 59.0(2), C1 C2 P2 Cu 39.0(2), Cu P3 C27 C28 48.6(2), P3 C27 C28 P4 49.6(3), C27 C28 P4 Cu
25.7(2).
3300
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 3293 – 3305

Inter- and Intramolecular Hydroamination of Unactivated Alkenes
and 0.05 mmol of 1,2-bis(diphenylphosphino)ethane in a
glove-box. Then 1.5 mL of 1,1’,2,2’-tetrachloroethane and
4 mmol of the corresponding alkene were added under a ni-
trogen atmosphere. After stirring at 100 or 1508C, the mix-
ture was filtered over CeliteTM, and the corresponding prod-
uct was isolated by flash chromatography.
Conclusions
The combined use of copper halides, phosphine li-
gands and silver salts was applied in the hydroamina-
tion of alkenes. Intermolecular reactions of unactivat-
ed olefins and nitrogen compounds of moderate nu-
cleophilicity were carried out successfully. Mechanis-
tic investigations demonstrated that the coordination
of the amine to the copper cationic complex was gen-
erating a Brønsted acid which was the prominent cat-
alytic species. Intramolecular reactions of electron-
rich amine derivatives were most likely following an
acid-catalysed pathway too. Hence, when a copper
halide in combination with a silver salt and a phos-
phane ligand catalyse the additions of weakly basic
amine substrates to olefins, it may be asked whether a
General Procedure (Amine Reactivities)
In a Schlenk flask, 1 mmol of the corresponding amine was
dried for one hour under vacuum (except for aniline which
was added at the end of the procedure). Then, 1 mmol of
norbornene, 0.05 mmol of CuBr2, 0.1 mmol of AgSbF6, and
0.05 mmol of 1,2-bis(diphenylphosphino)ethane were added
in a glove-box. 1.5 mL of 1,1’,2,2’-tetrachloroethane were
added under a nitrogen atmosphere. After stirring at 1008C,
the mixture was filtered over CeliteTM, and the correspond-
true metal-catalysed process is involved or if the ing product was isolated by flash chromatography.
N-1-Phenylpropan-2-yl-p-toluenesulfonamide (3e): Isolat-
ed after flash chromatography (petroleum ether:ethyl ace-
tate 8:2, Rf =0.1) as a colourless oil (from 1 mmol); yield:
252 mg (0.87 mmol, 88%). 1H NMR (CDCl3): d=1.10 (d,
J=6.5 Hz, 3H), 2.43 (s, 3H), 2.69 (dd, J=4.5 Hz, 2H), 3.53
(sep, J=6.5 Hz, 1H), 4.58 (d, J=6.5 Hz, 1H), 7.04 (d, J=
8.0 Hz, 2H), 7.24 (m, 5H), 7.64 (d, J=8.0 Hz, 2H);
13C NMR (CDCl3): d=21.3 (CH3), 21.5 (CH3), 43.4 (CH2),
50.9 (CH), 126.6 (CH), 127.0 (2CH), 128.5 (2CH), 129.4
(2CH), 129.6 (2CH), 137.1 (C), 137.6 (C), 143.1 (C); IR
(KBr): n=3323, 2965, 2927, 1313, 1157 cmÀ1; HR-MS (ESI):
m/z=290.12080, calcd. for C16H20O2NS (MH+): 290.12093.
N-2-(Pyridin-2-yl)ethyl-p-toluenesulfonamide (3f): Isolat-
ed after flash chromatography (petroleum ether:ethyl ace-
tate 1:1, Rf =0.1) as a white solid (from 1 mmol); yield:
metal simply generates a Brønsted acid.
Experimental Section
General Remarks
All solvents were dried using standard methods. Alkenes
were distilled under vacuum over CaH2 and stored over mo-
lecular sieves (4 ꢂ). Norbornene was sublimed under
vacuum and stored in a glove-box. Amine substrates were
placed under vacuum during one hour before use, or dis-
tilled over CaH2 if they were liquid. All silver salts, copper
salts and ligands were weighed in a glove-box. All reactions
were carried out under a dry nitrogen atmosphere. Analyti-
cal thin layer chromatography (TLC) was performed on
Merck pre-coated 0.20 mm silica gel Alugram Sil 60 G/
UV254 plates. Flash chromatography was carried out with
1
44 mg (0.16 mmol, 16%); mp 120–1228C; H NMR (CDCl3):
d=2.41 (s, 3H), 2.93 (t, J=6.3 Hz, 2H), 3.35 (q, J=6.3 Hz,
2H), 6.23 (t, J=5.7 Hz, 1H), 7.07 (dd, J=7.5, J=4.8 Hz,
1H), 7.14 (t, J=8.3 Hz, 1H), 7.26 (d, J=8.2 Hz, 2H), 7.58
(td, J=7.8, J=1.8 Hz, 1H), 7.72 (d, J=8.2 Hz, 2H), 8.46 (d,
J=4.5 Hz, 1H); 13C NMR (CDCl3): d=21.3 (CH3), 36.3
(CH2), 42.3 (CH2), 121.8 (CH), 123.5 (CH), 127.0 (2CH),
129.7 (2CH), 136.8 (CH), 137.1 (C), 143.2 (C), 149.1 (CH),
1
Macherey silica gel 60M. H (300 MHz), 13C (75 MHz) and
31P (121 MHz) NMR spectra were acquired on a Bruker
Avance spectrometer. Chemical shifts are reported down-
field of Me4Si and coupling constants are expressed in Hz.
1,3,5-Trimethoxybenzene and 1,2,4,5-tetrachlorobenzene
were used as internal standards when needed. Gas chroma-
tography analyses were done on GC Varian 3900 and 430
using an Alltech EconoCap EC-5TM 30 m column with pro-
gram (58CminÀ1, 100–2308C, 36 min) and with tetradecane
as internal standard. Infrared spectra were recorded on a
ThermoScientific-Nicolet 6700 spectrometer; the samples
being prepared with KBr powder. HPLC analysis was per-
formed on a Thermo-Finnigan 1000 apparatus with a diode
array detector. HR-MS analyses were performed at CUMA
– Pharm. Dept. – University Lille Nord de France. Elemen-
tal analyses on sensitive samples were performed at London
Metropolitan University, UK. Elemental analyses on other
samples were performed at UCCS, University Lille Nord de
France, France. See the Supporting Information for other
details.
158.9 (C); IR (KBr): n=3063, 2956, 2864, 1324, 1155 cmÀ1
;
HR-MS (ESI): m/z=277.1003, calcd. for C14H17O2N2S
(MH+): 277.1005; anal. calcd. (%) for C14H16O2N2S: C 60.85,
H 5.84, N 10.14, S 11.60; found: C 60.90, H 5.81, N 10.78, S
11.13.
N-Bicyclo
ACHTUNGTREN[NGNU 2.2.1]hept-2-yl-2-chloroacetamide (5b): Isolated
after flash chromatography (petroleum ether:ethyl acetate
8:2) as
a white solid (from 1 mmol); yield: 135 mg
(0.72 mmol, 72%); mp 123–1258C; 1H NMR (CDCl3): d=
1.00–1.30 (m, 5H), 1.35–1.55 (m, 2H), 1.85 (m, 1H), 2.17
(m, 1H), 2.25 (m, 1H), 3.66 (td, J=3.5, J=7.8 Hz, 1H), 3.95
(s, 2H), 6.34 (s, 1H, NH); 13C NMR (CDCl3): d=26.4
(CH2), 28.1 (CH2), 35.6 (CH2), 35.7 (CH), 40.2 (CH2, C),
42.2 (CH), 42.6 (CH2), 53.1 (CH), 164.9 (CO); IR (KBr):
n=3291, 2870, 1655, 1549 cmÀ1
; anal. calcd. (%) for
C9H14ClNO: C 57.60, H 7.52, N 7.46; found: C 57.15, H
7.21, N 7.10.
N-BicycloACTHNUTRGENUG[N 2.2.1]hept-2-yl-carbamic acid benzyl ester (5c):
General Procedure (Olefin Reactivities)
To a Schlenk flask were added 1 mmol of toluenesulfon-
Isolated after flash chromatography (petroleum ether:ethyl
A
acetate 8:2, Rf =0.6) as a white solid (from 1 mmol); yield:
195 mg (0.80 mmol, 80%; mp 148–1508C; H NMR (CDCl3):
1
Adv. Synth. Catal. 2010, 352, 3293 – 3305
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3301

Christophe Michon et al.
FULL PAPERS
d=1.05–1.40 (m, 5H), 1.50 (m, 2H), 1.70–1.85 (m, 1H),
2.20–2.35 (m, 2H), 3.50–3.60 (m, 1H), 4.70 (s, 1H, NH), 5.1
(s, 2H, CH2), 7.30–7.45 (m, 5H); 13C NMR (CDCl3): d=26.3
(CH2), 28.1 (CH2), 35.3 (CH2), 35.6 (CH), 40.4 (CH2), 42.5
(CH), 54.3 (CH), 66.5 (CH2), 128.1 (2CH), 128.2 (CH),
128.5 (2CH), 136.6 (C), 155.6 (C); IR (KBr): n=3299, 2956,
2870, 1682, 1545, 1256 cmÀ1; HR-MS (ESI): m/z=246.1487,
calcd. for C15H20O2N (MH+): 246.1489; anal. calcd. (%) for
C15H19O2N: C 73.44, H 7.81, N 5.71; found: C 72.91, H 7.89,
N 5.47.
yield: 0.08 g (40%); 1H NMR (CD2Cl2): d=2.16 (s, 2H,
CH2), 2.47 (s, 3H, Me), 4.87 (s broad, 1H, NH), 7.22 (m,
3
2H), 7.36 (d, 2H, J=8.1 Hz, HTos), 7.48 (m, 4H), 7.69 (m,
3
4H), 7.81 (d, 2H, J=8.1 Hz, HTos); 31P NMR (CD2Cl2): d=
50.04; 13C NMR (CD2Cl2): d=21.2, 29.7, 126.3, 129.1, 129.6,
129.7, 130.4, 131.0, 131.6, 132.1ACTHNUGTRNEUNG(2C), 132.7, 138.9, 143.9; IR
(KBr, inert cell): n=3360 (s), 3260 (s), 1304 (vs), 1160 cmÀ1
(s); anal. calcd. (%) for C33H32F6O2P2NSCuSb: C 45.67, H
3.72, N 1.61; found: C 45.44, H 3.61;,N, 1.75.
N-BicycloACHTUNGTRENNUNG[2.2.1]hept-2-yl-2H-benzo[d]ACHTUNTGNER[NUGN 1,2,3]triazole (5f1):
AHCTUNGTRENNUNG
Isolated by flash chromatography (petroleum ether:ethyl
acetate 80:20, Rf =0.7) as a white solid (from 1 mmol);
yield: 30 mg (0.14 mmol, 14%); mp 45–478C; 1H NMR
(300 MHz, CDCl3): d=1.20–1.80 (m, 7H), 2.50–2.85 (m,
3H), 4.88 (dd, J=4.2 Hz, J=8.5, 1H), 7.39 (m, 2H), 7.89
(m, 2H); 13C NMR (75 MHz, CDCl3): d=27.1 (CH2), 28.5
(CH2), 35.8 (CH2), 36.1 (CH), 38.2 (CH2), 44.1 (CH), 69.4
(CH), 118.0 (2CH), 126.0 (2CH), 143.9 (2C); IR: n=2955,
2870, 1277 cmÀ1; HR-MS (ESI): m/z=214.13374, calcd. for
C13H16N3 (MH+): 214.13387; anal. calcd. (%) for C13H15N3:
C 73.21, H 7.09, N 19.70; found: C 72.69, H 7.09, N 20.34.
AHCTUNGTRENNUNG
AHCTUNGTRENN(GUN IPr)CuCl (0.05 g, 0.1 mmol) was combined with AgSbF6
(0.036 g, 0.1 mmol) in 4 mL THF. After stirring for 1 hour,
AgCl was removed by filtration through dry CeliteTM, and
the filtrate was concentrated under vacuum to approximate-
ly 2 mL and transferred to a 4 mL THF solution of 4-nitro-
AHCTUNGTREGaNNUN niline (0.014 g, 0.1 mmol). The resulting solution was
heated to 608C under nitrogen for one hour. Evaporation to
dryness afforded a yellow solid; yield: 0.074 g (90%);
1H NMR (CD2Cl2): d=1.17 [d, J=7.0 Hz, 12H, CH
(CH3)2],
3
N-BicycloACHTUNGTRENNUNG[2.2.1]hept-2-yl-1H-benzo[d]ACHTUNTGNER[NUGN 1,2,3]triazole (5f2):
3
3
Isolated by flash chromatography (petroleum ether:ethyl
acetate 80:20, Rf =0.3) as a white solid (from 1 mmol);
yield:, 46 mg (0.21 mmol, 21%); mp 75–778C; 1H NMR
(300 MHz, CDCl3): d=1.30–2.10 (m, 7H), 2.50–2.80 (m,
3H), 4.60 (dd, J=3.8, J=8.4 Hz, 1H), 7.36 (m, H), 7.47 (t,
H), 7.56 (d, J=8.3 Hz, H), 8.07 (d, J=8.3 Hz, H); 13C NMR
(75 MHz, CDCl3): d=27.1 (CH2), 28.7 (CH2), 35.9 (CH2),
36.0 (CH), 37.3 (CH2), 42.9 (CH), 61.9 (CH), 109.7 (CH),
119.9 (CH), 123.8 (CH), 126.8 (CH), 133.0 (C), 146.3 (C);
1.24 [d, J=7.0 Hz, 12H, CH
4H, CH(CH3)2], 5.08 (s, 2H, NH2), 6.70 (d, J=9.2 Hz, 2H,
ACHTUNGTERN(NNUG CH3)2], 2.47 (sept, J=7.9 Hz,
3
AHCTUNGTRENNUNG
CH 4-nitroaniline), 7.32 (m, 6H, NCH + CH IPr p-phenyl),
7.57 (t, J=7.7 Hz, 2H), 7.99 (d, 3J=9.2 Hz, 2H, CH 4-nitro-
3
aniline); 13C NMR (CD2Cl2): d=176.5 ( NCN), 145.5, 144.3,
133.9, 130.9, 125.7, 124.4
G
ACHTUNGTRENNUNG(CH3)2],
24.6 [CH(CH3)2], 23.6 [CH
C33H43F6N4O2CuSb: C 47.93, H 5.24, N 6.77; found: C 47.81,
H 5.11, N 6.65.
G
ACHTUNGTRENNUNG
IR: n=2963, 2868, 1454 cmÀ1
; HR-MS (ESI): m/z=
214.1338, calcd. for C13H16N3 (MH+): 214.13387; anal. calcd.
(%) for C13H15N3: C 73.21, H 7.09, N 19.70; found: C 73.64,
H 7.47, N 20.14.
Bis
ACHTUNGTRENNUNG
fluoroantimonate [(dppe)2Cu]AHCTNUGTRENNNUG
CuBr (0.067 g, 0.47 mmol), diphenylphosphinoethane
(0.37 g, 0.94 mmol) and AgSbF6 (161 mg, 0.47 mmol) were
dissolved in 5 mL dichloromethane. After stirring for 3 h
under nitrogen at room temperature, AgCl was removed by
filtration through dry CeliteTM under nitrogen and the fil-
trate was evaporated to dryness to afford a white solid;
yield: 0.486 g (95%); 1H NMR (CD2Cl2): d=2.48 (m, 8H,
CH2), 7.25 (m, 29H, HAr), 7.41 (m, 10H, HAr); 31P NMR
(CD2Cl2): d=7.24 (very broad singlet), 4.17 (d, J=17.8 Hz),
2.11 (d, J=17.7 Hz); anal. calcd. (%) for C52H48F6P4CuSb: C
56.98, H 4.41; found: C 56.90, H 4.30.
N-BicycloACHTUNGTRENNUNG[2.2.1]hept-2-yl-oxazolidin-2-one (5g): Isolated
after flash chromatography (petroleum ether:acetone 7:3,
Rf =0.6) as colourless oil (from 1 mmol); yield:173 mg
1
(0.95 mmol, 95%); H NMR (CDCl3): d=1.30 (m, 4H), 1.50
(m, 3H), 1.78 (m, 1H), 2.25 (s, 1H), 2.31 (s, 1H), 3.55 (m,
2H), 3.78 (dd, J=8, J=5 Hz, 1H), 4.20–4.35 (m, 2H);
13C NMR (CDCl3): d=27.7 (CH2), 28.0 (CH2), 36.0 (CH),
36.6 (CH2), 36.7 (CH2), 40.5 (CH), 42.1 (CH2), 56.4 (CH),
61.8 (CH2), 158.2 (CO); IR (KBr): n=2870, 1743,
1263 cmÀ1
;
HR-MS (ESI): m/z=182.1177, calcd. for
C10H16O2N (MH+): 182.1176.
[Diphenylphosphinoethano][4-methylbenzenesulfon-
amidato-k-N-]copper(I) Hexafluoroantimonate
[dppeCuNHTos]ACHTUNGTRENNUNG[SbF6] (6)
Acknowledgements
CuBr2 (0.052 g, 0.23 mmol), 1,2-bis(diphenylphosphino)-
ethane (0.093 g, 0.23 mmol) and AgSbF6 (0.16 mg,
0.46 mmol) were dissolved in 5 mL dichloromethane. After
stirring for 3 h under nitrogen at room temperature, AgCl
was removed by filtration through CeliteTM under nitrogen
and the filtrate was allowed to react for 20 min (10 min ul-
trasonic bath+10 min stirring at room temperature) with to-
sylamine (0.04 g, 0.23 mmol). Evaporation to dryness afford-
ed a grey solid which was recrystallised two times using
CH2Cl2 and pentane then dried affording a white solid;
This work is first financed by the French National Research
Agency with project ANR-09-BLAN-0032-02 (with a PhD
fellowship to F.M). Support from CNRS is warmly acknowl-
edged. Partial funding from Rꢀgion Nord-Pas de Calais
with“Projet Prim: Etat-Rꢀgion” is also appreciated. Dr. I.
Suisse is thanked for preliminary experiments. Mrs. C. Mꢀliet
is thanked for elemental analyses on organic samples. The
authors are grateful to the reviewers for their comments.
3302
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 3293 – 3305

Inter- and Intramolecular Hydroamination of Unactivated Alkenes
References
Xia, H. Wei, B. Xu, C. Zhang, Y. Li, G. Qian, X.
Zhang, K. Li, W. Li, Eur. J. Org. Chem. 2008, 1929–
1936; e) Bi:H. Wei, Q. Gumin, Y. Xia, K. Li, Y. Li, W.
Li, Eur. J. Org. Chem. 2007, 4471–4474; f) Bi, Hf: H.
Qin, N. Yamagiwa, S. Matsunaga, M. Shibasaki, Chem.
Asian J. 2007, 2, 150–154; g) In: J. M. Huang, C. M.
Wong, F. X. Xu, T. P. Loh, Tetrahedron Lett. 2007, 48,
3375–3377; h) Fe: J. Michaux, V. Terrasson, S. Marque,
J. Wehbe, D. Prim, J. M. Campagne, Eur. J. Inorg.
Chem. 2007, 2601–2603; i) Fe: K. Komeyama, T. Mori-
moto, K. Takaki, Angew. Chem. 2006, 118, 3004–3007;
Angew. Chem. Int. Ed. 2006, 45, 2938–2941; j) Bi: H.
Qin, N. Yamagiwa, S. Matsunaga, M. Shibasaki, J. Am.
Chem. Soc. 2006, 128, 1611–1614.
[1] a) J. J. Brunet, D. Neibecker, in: Catalytic Heterofunc-
tionalization from Hydroamination to Hydrozircona-
tion, (Eds.: A. Togni, H. Grutzmacher), Wiley-VCH,
Weinheim, Germany, 2001, pp 10–20; b) S. Doye, in:
Science of Synthesis, Vol. 40a, (Eds.: D. Enders, E.
Schaumann), Thieme, Stuttgart, 2009, pp 241–304;
c) U. M. Dzhemilev, G. A. Tolstikov, R. I. Khusnutdi-
nov, Russ. J. Org. Chem. 2009, 45, 957–987; d) T. E.
Mueller, K. C. Hultzsch, M. Yus, F. Foubelo, M. Tada,
Chem. Rev. 2008, 108, 3795–3892; e) I. Aillaud, J.
Collin, J. Hannedouche, E. Schulz, Dalton Trans. 2007,
5105–5118; f) K. C. Hultzsch, Adv. Synth. Catal. 2005,
347, 367–391; g) A. L. Odom, Dalton Trans. 2005, 225–
233; h) I. Bytschkov, S. Doye, Eur. J. Org. Chem. 2003,
935–946; i) P. W. Roesky, T. E. Mꢃller, Angew. Chem.
2003, 115, 2812–2814; Angew. Chem. Int. Ed. 2003, 42,
2708–2710; j) T. E. Mꢃller, M. Beller, Chem. Rev. 1998,
98, 675–703.
[5] For selected examples of heterogeneous Brønsted acid
hydroamination of alkenes: a) D. P. Sawant, J. Justus,
V. V. Balasubramanian, K. Ariga, P. Srinivasu, S. Vel-
mathi, S. B. Halligudi, A. Vinu, Chem. Eur. J. 2008, 14,
3200–3212; b) L. Yang, L. W. Xu, C. G. Xia, Tetrahe-
dron Lett. 2008, 49, 2882–2885; c) J. S. Yadav, B. V. S.
Reddy, A. Raju, K. Ravindar, R. Narender, Lett. Org.
Chem. 2008, 5, 651–654; d) G. V. Shanbhag, S. M.
Kumbar, S. B. Halligudi, J. Mol. Catal. A Chem. 2008,
284, 16–23; e) K. Motokura, N. Nakagiri, K. Mori, T.
Mizugaki, K. Ebitani, K. Jitsukawa, K. Kaneda, Org.
Lett. 2006, 8, 4617–4620; f) O. Jimenez, T. E. Mꢃller,
C. Sievers, A. Spirkl, J. A. Lercher, Chem. Commun.
2006, 2974–2976; g) M. Lequitte, F. Figueras, C.
Moreau, S. Hub, J. Catal. 1996, 163, 255–261; h) N.
Mizuno, M. Tabata, T. Uematsu, M. Iwamoto, J. Catal.
1994, 146, 249–256; i) M. Deeba, M. E. Ford, T. A.
Johnson, J. Chem. Soc. Chem. Commun. 1987, 562–
563.
[6] For selected examples of homogeneous Brønsted acid
hydroamination of alkenes: a) amides: C. M. Griffiths-
Jones (nꢀe Haskins), D. W. Knight, Tetrahedron 2010,
66, 4150–4166; b) amides, anilines: L. Yang, L. W. Xu,
C. G. Xia, Synthesis 2009, 1969–1974; c) basic amines:
L. Ackermann, A. Althammer, Synlett 2008, 995–998;
d) basic amines: L. Ackermann, L. T. Kaspar, A. Al-
thammer, Org. Biomol. Chem. 2007, 5, 1975–1978;
e) anilines: K. Mꢄrcsekova, S. Doye, Synthesis 2007,
145–154; f) anilines: N. S. Babu, K. M. Reddy, P. S. S.
Prasad, I. Suryanarayana, N. Lingaiah, Tetrahedron
Lett. 2007, 48, 7642–7645; g) amides: Y. Yin, G. Zhao,
J. Fluorine Chem. 2007, 128, 40–45; h) amides: D. C.
Rosenfeld, S. Shekhar, A. Takemiya, M. Utsunomiya,
J. F. Hartwig, Org. Lett. 2006, 8, 4179–4182; i) amides:
Z. Li, J. Zhang, C. Brouwer, C. G. Yang, N. W. Reich,
C. He, Org. Lett. 2006, 8, 4175–4178; j) anilines:
A. A. M. Lapis, B. A. DaSilveira Neto, J. D. Scholten,
F. M. Nachtigall, M. N. Eberlin, J. Dupont, Tetrahedron
Lett. 2006, 47, 6775–6779; k) amides: Y. Yin, G. Zhao,
Heterocycles 2006, 68, 23–31; l) anilines: L. L. Ander-
son, J. Arnold, R. G. Bergman, J. Am. Chem. Soc. 2005,
127, 14542–14543, and references cited therein; m) ani-
lines: A. E. Cherian, G. J. Domski, J. M. Rose, E. B.
Lobokovsky, G. W. Coates, Org. Lett. 2005, 7, 5135–
5137; n) amides: C. M. Haskins, D. W. Knight Chem.
Commun. 2005, 3162–3164; o) amides: S. K. Talluri, A.
Sudalai, Org. Lett. 2005, 7, 855–857; p) amides: P. A.
Colinas, R. D. Bravo, Org. Lett. 2003, 5, 4509–4511;
[2] a) J. Guin, R. Frçhlich, A. Studer, Angew. Chem. 2008,
120, 791–794; Angew. Chem. Int. Ed. 2008, 47, 779–
782; b) J. Guin, C. Mꢃck-Lichtenfeld, S. Grimme, A.
Studer, J. Am. Chem. Soc. 2007, 129, 4498–4503.
[3] For selected examples of metal-acid catalysed hydro-
ACHTUNGTRENNUNGamination of alkenes: a) H. Kitahara, H. Sakurai,
Chem. Lett. 2010, 39, 46–48; b) P. A. Dub, M. Rodri-
gues-Zubiri, C. Baudequin, R. Poli, Green Chem. 2010,
12, 1392–1396; c) J. L. McBee, A. T. Bell, T. D. Tilley,
J. Am. Chem. Soc. 2008, 130, 16562–16571; d) C. F.
Bender, R. A. Widenhoefer, Chem. Commun. 2008,
2741–2743; e) B. M. Cochran, F. E. Michael, J. Am.
Chem. Soc. 2008, 130, 2786–2792; f) W. J. Shi, Y. Liu, P.
Butti, A. Togni, Adv. Synth. Catal. 2007, 349, 1619–
1623; g) L. T. Kaspar, B. Fingerhut, L. Ackermann,
Angew. Chem. 2005, 117, 6126–6128; Angew. Chem.
Int. Ed. 2005, 44, 5972–5974; h) D. Karshtedt, A. T.
Bell, T. D. Tilley, J. Am. Chem. Soc. 2005, 127, 12640–
12646; i) L. Ackermann, L. T. Kaspar, C. J. Gschrei,
Org. Lett. 2004, 6, 2515–2518; j) T. C. Wabnitz, J. Q.
Yu, J. B. Spencer Chem. Eur. J. 2004, 10, 484–493;
k) L. L. Anderson, J. Arnold, R. G. Bergman, Org.
Lett. 2004, 6, 2519–2522; l) J. Penzien, R. Q. Su, T. E.
Mꢃller, J. Mol. Catal. A: Chem. 2002, 182–183, 489–
498; m) R. Q. Su, T. E. Mꢃller, Tetrahedron 2001, 57,
6027–6033; n) M. Kawatsura, J. F. Hartwig, J. Am.
Chem. Soc. 2000, 122, 9546–9547; o) M. Beller, O. R.
Thiel, H. Trauthwein, Synlett 1999, 243–244; p) M. Al-
Masum, M. Meguro, Y. Yamamoto, Tetrahedron Lett.
1997, 38, 6071–6074; q) M. Beller, H. Trauthwein, M.
Eichberger, C. Breindl, J. Herwig, T. E. Mꢃller, O. R.
Thiel, Chem. Eur. J. 1999, 5, 1306–1319; r) J. J. Brunet,
D. Commenges, D. Neibecker, K. Philippot, J. Organo-
met. Chem. 1994, 469, 221–228; s) J. Ambꢃhl, P. S. Pre-
gosin, L. M. Venanzi, G. Ughetto, L. Zambonelli, J. Or-
ganomet. Chem. 1978, 160, 329–335.
[4] For selected examples of Lewis acid catalysed hydroa-
mination of alkenes: a) Ga: D. Jaspers; R. Kubiak, S.
Doye, Synlett 2010, 1268–1272; b) Bi: N. Kawai, R.
Abe, J. Uenishi, Tetrahedron Lett. 2009, 50, 6580–6583;
c) Zr: L. Yang, L. W. Xu, W. Zhou, Y. H. Gao, W. Sun,
C. G. Xia, Synlett 2009, 1167–1171; d) X. Cheng, Y.
Adv. Synth. Catal. 2010, 352, 3293 – 3305
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3303

Christophe Michon et al.
FULL PAPERS
q) amides: B. Schlummer, J. F. Hartwig, Org. Lett. 2002,
4, 1471–1474; r) amides: C. M. Haskins, D. W. Knight,
Chem. Commun. 2002, 2724–2725.
[19] a) M. J. S. Dewar, Bull. Soc. Chim. Fr. 1951, 18, C71-
C79; b) J. Chatt, L. A. Duncanson, J. Chem. Soc. 1953,
2939–2947; c) C. Hahn, Chem. Eur. J. 2004, 10, 5888–
5899.
[20] a) P. Lazlo, P. v. R. Schleyer J. Am. Chem. Soc. 1964,
86, 1171–1179; b) J. E. Franz, C. Osuch, M. W. Dietrich
J. Org. Chem. 1964, 29, 2922–2927.
[21] a) C. Q. Zhao, M. C. Jennings, R. J. Puddephat, Inorg.
Chim. Acta 2008, 361, 3301–3308; b) K. N. Lazarou,
S. P. Perlepes, V. Psycharis, C. P. Raptopoulou, Poly-
hedron 2008, 27, 2131–2142.
[22] a) J. Moran, P. H. Cebrowski, A. M. Beauchemin, J.
Org. Chem. 2008, 73, 1004–1007; b) A. R. Katritzky,
I. B. Puschmann, C. V. Stevens, A. P. Wells, J. Chem.
Soc. Perkin Trans. 2 1995, 1645–1649.
[23] For selected examples of hydroamination-hydroaryla-
tion of alkynes: a) N. T. Patil, P. G. V. V. Lakshmi, V.
Singh, Eur. J. Org. Chem. 2010, 4719–4731; b) Y. Zhou,
E. Feng, G. Liu, D. Ye, J. Li, H. Jiang, H. Liu, J. Org.
Chem. 2009, 74, 7344–7348; c) N. T. Patil, R. D.
Kavthe, V. S. Raut, V. V. N. Reddy, J. Org. Chem. 2009,
74, 6315–6318; d) X. Y. Liu, P. Ding, J. S. Huang, C. M.
Che, Org. Lett. 2007, 9, 2645–2648; e) N. Pasha, N. S.
Babu, K. T. V. Rao, P. S. Prasad, N. Lingaiah, Tetrahe-
dron Lett. 2009, 50, 239–242; f) R. Severin, S. Doye,
Chem. Soc. Rev. 2007, 36, 1407–1420; g) F. Pohlki, S.
Doye, Chem. Soc. Rev. 2003, 32, 104–114.
[7] a) Z. Zhang, S. D. Lee, R. A. Widenhoefer, J. Am.
Chem. Soc. 2009, 131, 5372–5373; b) X. Giner, C.
Najera, Org. Lett. 2008, 10, 2919–2922; c) M. Shi, L. P.
Liu, J. Tang, Org. Lett. 2006, 8, 4043–4046; d) J. Zhang,
C. G. Yang, C. He, J. Am. Chem. Soc. 2006, 128, 1798–
1799; e) C. Brouwer, C. He, Angew. Chem. 2006, 118,
1776–1779; Angew. Chem. Int. Ed. 2006, 45, 5, 1744–
1747; f) X. Y. Liu, C. H. Li, C. M. Che, Org. Lett. 2006,
8, 2707–2710; g) M. C. P. Yeh, H. F. Pai, Z. J. Lin, B. R.
Lee, Tetrahedron 2009, 65, 4789–4794; h) H. Kitahara,
H. Sakurai, Chem. Lett. 2010, 39, 46–48.
[8] a) R. L. LaLonde, Z. J. Wang, M. Mba, A. D. Lackner,
F. D. Toste, Angew. Chem. 2010, 122, 608–611; Angew.
Chem. Int. Ed. 2010, 49, 598–601; b) K. Aikawa, M.
Kojima, K. Mikami, Angew. Chem. 2009, 121, 6189–
6193; Angew. Chem. Int. Ed. 2009, 48, 6073–6077; c) Z.
Zhang, C. F. Bender, R. A. Widenhoefer, J. Am. Chem.
Soc. 2007, 129, 14148–14149; d) G. L. Lalonde, B. D.
Sherry, E. J. Kang, F. D. Toste, J. Am. Chem. Soc. 2007,
129, 2452–2453; e) N. Nishina, Y. Yamamoto, Angew.
Chem. 2006, 118, 3392–3395; Angew. Chem. Int. Ed.
2006, 45, 3314–3317; f) N. T. Patil, L. M. Lutete, N.
Nishina, Y. Yamamoto, Tetrahedron Lett. 2006, 47,
4749–4751.
[24] a) H. Tang, N. Arulsamy, M. Radosz, Y. Shen, N. V.
Tsarevsky, W. A. Braunecker, W. Tang, K. Matyjaszew-
ski, J. Am. Chem. Soc. 2006, 128, 16277–16285;
b) M. J. L. Tschan, C. M. Thomas, H. Strub, J. F. Car-
pentier, Adv. Synth. Catal. 2009, 351, 2496–2505;
c) K. E. Nosova, E. V. Tretyakov, G. V. Romanenko,
V. I. Ovcharenko, Russ. Chem. Bull. Int. Ed. 2003, 52,
2231–2234.
[25] E. D. Blue, A. Davis, D. Conner, T. B. Gunnoe, P. D.
Boyle, P. S. White, J. Am. Chem. Soc. 2003, 125, 9435–
9441.
[26] CCDC 783449 for 10 and CCDC 783450 for 11. These
data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
[27] a) J. J. Allen, A. R. Barron, Dalton Trans. 2009, 878–
890; b) A. Boni, G. Pampaloni, R. Peloso, D. Belleti, C.
Graiff, A. Tiripicchio, J. Organomet. Chem. 2006, 691,
5602–5609; c) B. F. Straub, I. Gruber, F. Rominger, P.
Hofmann, J. Organomet. Chem. 2003, 684, 124–143;
d) B. F. Straub, F. Eisentrꢅger, P. Hofmann, Chem.
Commun. 1999, 2507–2508; e) J. Min, J. Benet-Buch-
holz, R. Boese, Chem. Commun. 1998, 2751–2752;
f) D. D. LeCloux, R. Davydov, S. J. Lippard, Inorg.
Chem. 1998, 37, 6814–6826; g) M. Pasquali, C. Floriani,
A. Gaetani-Manfredotti, A. Chiesi-Villa, J. Am. Chem.
Soc. 1978, 100, 4918–4919.
[28] a) C. Di Nicola, C. Pettinari, M. Ricciutelli, B. W. Skel-
ton, N. Somers, A. H. White, Inorg. Chim. Acta 2005,
258, 4003–4008; b) K. H. Lin, Q. Xie, R. N. Yang, L. P.
Xing, D. M. Jin, Jiegou Huaxue 2002, 21, 51–54; c) P.
Comba, C. Katsichtis, B. Nuber, H. Pritzkow, Eur. J.
Inorg. Chem. 1999, 777–783.
[9] X. Giner, C. Najera, Synlett 2009, 3211–3213.
[10] a) B. Zhao, H. Du, Y. Shi, J. Org. Chem. 2009, 74,
8392–8395; b) H. Du, B. Zhao, W. Yuan, Y. Shi, Org.
Lett. 2008, 10, 4231–4234.
[11] a) E. S. Sherman, S. R. Chemler, Adv. Synth. Catal.
2009, 351, 467–471; b) W. Zeng, S. R. Chemler, J. Org.
Chem. 2008, 73, 6045–6047.
[12] a) J. G. Tayor, L. A. Adrio, K. K. Hii, Dalton Trans.
2010, 39, 1171–1175; b) J. G. Taylor, N. Whittall, K. K.
Hii, Org. Lett. 2006, 8, 3561–3564.
[13] a) C. Munro-Leighton, S. A. Delp, E. D. Blue, T. B.
Gunnoe, Organometallics 2007, 26, 1483–1493; b) C.
Munro-Leighton, E. D. Blue, T. B. Gunnoe, J. Am.
Chem. Soc. 2006, 128, 1446–1447.
[14] H. Ohmiya, T. Moriya, M. Sawamura, Org. Lett. 2009,
11, 2145–2147.
[15] a) J. J. Brunet, D. Neibecker, F. Agbossou, S. S. Radhey,
J. Mol. Catal. 1994, 87, 223–230; b) J. J. Brunet, D. Nei-
becker, F. Niedercorn, J. Mol. Catal. 1989, 49, 235–259.
[16] For selected examples of copper-olefin complexes:
a) P. O. Oguadinma, F. Schaper, Organometallics 2009,
28, 6721–6731; b) J. S. Thompson, A. Z. Bradley, K. H.
Park, K. D. Dobbs, W. Marshall, Organometallics 2006,
25, 2712–2714; c) G. Pampaloni, R. Peloso, C. Graiff,
A. Tiripicchio, Organometallics 2005, 24, 819–825;
d) W. A. Braunecker, T. Pintauer, N. V. Tsarevsky, G.
Kickelbick, K. Matyjaszewski, J. Organomet. Chem.
2005, 690, 916–924; e) P. Kamau, R. B. Jordan, Inorg.
Chem. 2002, 41, 884–891.
[17] a) R. Dias, J. Wu, Eur. J. Inorg. Chem. 2008, 509–522;
b) J. S. Thompson, R. L. Harlow, J. F. Whitney, J. Am.
Chem. Soc. 1983, 105, 3522–3527.
[18] A. Tsuhako, D. Oikawa, K. Sakai, S. Okamoto, Tetrahe-
[29] For selected examples of the hemilability of copper,
dron Lett. 2008, 49, 6529–6532.
see: a) A. Boni, G. Pampaloni, R. Peloso, D. Belleti, C.
3304
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 3293 – 3305

Inter- and Intramolecular Hydroamination of Unactivated Alkenes
Graiff, A. Tiripichio, J. Organomet. Chem. 2006, 691,
5602–5609; b) J. S. Lewis, J. Zweit, P. J. Blower, Poly-
hedron 1998, 17, 513–517; c) C. Pettinari, F. Marchetti,
R. Polimante, A. Cingolani, G. Portalone, M. Colapie-
tro, Inorg. Chim. Acta 1996, 249, 215–229.
Adv. Synth. Catal. 2010, 352, 3293 – 3305
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3305